1. Field of the Invention
The present invention relates to articles that have an antimicrobial coating.
2. Description of the Related Art
The ability of bacteria to colonize the surface of plastics, ceramics and metals is a serious problem in modern medicine. Articles implanted in patients, such as drainage tubes, stents, vascular prostheses, dental prostheses, cardiac valves, limb prostheses, contact lenses, artificial lenses and surgical suture materials, are prone to colonization by bacteria. Catheters, in particular, are preferred sites of colonization for bacteria (e.g. D A Goldmann and G B Pier, Clin. Microbiol. Rev. 6, 176192, 1993). When these articles act as a culture medium for antibiotic resistant bacteria, they put a patient at risk for developing an uncontrollable infection. Increasing numbers of antibiotic resistant bacteria have created an urgent need for articles nearly free of bacterial contamination (A G Gristina et al., Biomaterials, 8, 423426, 1987).
Several approaches have already been tried to prevent bacteria from colonizing on the surfaces of medical articles. Silver compounds (e.g. silver nitrate, silver zeolite and silver sulfadiazine) have been used as antibacterial agents in plastic catheters (EP 328 421, JA 03244663, J. Infectious Diseases 167, 920-924, 1992).
There have also been attempts to treat articles with high concentrations of antibiotics in order to prevent bacteria from colonizing on their surfaces. Antibiotics such as gentamycin, rifamycin, and ciprofloxacin have been used (J M Schierholz, Hospitalis 65, 403-407, 1995), as well as antiseptics such as biguanidines, iodine and/or chlorohexidine (G Golomb and A Shpigelman, J. Biomed. Mat. Res., 25, 937-952, 1991). For these compounds to be effective in preventing bacteria growth, they must be present at concentrations of 0.1 to 2% around the article surface. At these concentrations, the antibiotics and antiseptics will damage human tissues and cells. Moreover, when these articles come in contact with bodily fluids, the concentrations of antibiotics and antiseptics around the article surface will quickly drop below the level necessary for preventing bacterial growth. None of these approaches have shown promise in suppressing bacterial colonization on medical devices.
In addition to being susceptible to bacterial contamination, medical devices used as implants can cause dangerous blood clots. The clots are started when blood cells and other blood particles, such as thrombocytes, adhere to the surface of the implanted device. While certain disinfectants (e.g. benzalkonium chloride/heparin) have been shown to reduce the incidence of clotting, they have poor adherence to plastic, ceramic, and metal, and quickly dissolve off the surface of the implanted device.
Tissues can also adhere to an implant device, causing dangerous medical problems. For example, surgical procedures for inserting an intravascular catheter into a patient's blood vessel are complicated by the tendency of the vessel wall to grip the catheter surface. The resulting friction can cause a tear in the delicate inner lining of the vessel wall, and lead to the formation of a potentially deadly thrombus. Accordingly, the development of coatings that adhere to the surfaces of implantable medical devices, but not to blood cells and tissues, is an important goal for making safe implants.
Articles that can remain free from bacterial contamination would be useful in many applications in addition to medical devices. Pharmaceutical research with genetically engineered microbes, for example, requires large amounts of laboratory equipment to be exposed to experimental microbes. Savings in decontamination costs, as well as increased safety, would be realized if the equipment used in this research (e.g. containers, pipelines, bottles, pipettes, etc.) does not promote the growth of the contaminating microbes.
Cost could also be reduced by providing water treatment plants that resist bacterial growth. Presently, it is common for unchecked bacterial growth to clog and corrode waste water treatment plants. Plants that are built with equipment that can resist bacterial growth would last longer and require less maintenance. This equipment includes pipes, pumps, screens, and waste storage containers.
Sanitary conditions could also be enhanced by providing articles resistant to bacterial growth that are used to handle food and beverages. Also, the spreading of communicable disease would be reduced by providing bacterial resistant articles (e.g. seats, telephones, and toilets, doorknobs, handles, latches, etc.) in public places like airports, schools and hospitals.